First report of syn isomers in the diastereoselective synthesis of highly functionalized piperidines catalysed by wet picric acid: factors influencing the syn-anti ratios

This is the first report of the formation of a syn-diastereoisomer in the diastereoselective synthesis of highly functionalized piperidines catalysed by wet picric acid via a one-pot, step-economic condensation of aromatic aldehydes, 1,3-dicarbonyl compounds and aromatic amines. DFT calculation shows that anti isomers are more stable compared to the syn. The syn-anti ratio of the products depends on the temperature and the nature of substitution on both the aromatic aldehydes and aromatic amines. Conditions for getting pure anti and pure syn compounds have been studied.     

Influence of the side chain protecting group on the stereoselectivity of the 1,3-dipolar cycloaddition of d-talo-configured nitrones

Two new five-membered cyclic d-talo-configured nitrones were synthesized from d-mannose, and examined in 1,3-dipolar cycloadditions with vinyl acetate and vinylene carbonate. The stereoselectivity of the cycloadditions depends greatly on the protecting group of the vicinal diol attached to the nitrone C-5 carbon atom. Methyl protection resulted in limited syn/anti-selectivity, giving mixtures of the two isomeric exo-syn and exo-anti isoxazolidines in comparable amounts. On the other hand, the cyclohexylidene-substituted nitrone reacted more selectively in favour of the syn isomer. The difference in the diastereoselectivity was attributed to the specific spatial orientation of the nitrone C-5 substituent.     

The reaction of a monochlorocarbenoid with some methoxycycloalkenes—an observation on the mechanism of the insertion reaction of carbenes and carbenoids into double bonds

The products from the reaction of the monochlorocarbenoid, derived from butyl lithium and dichloromethane, on 3- and 4-methoxycyclohexene and 3- and 4-methoxycyclopentene were examined. The major products have the chlorocyclopropane ring syn to the OMe group. In the products from the 4-methoxycycloalkenes the major syn product has the chloro group exo, the 3-methoxycycloalkenes are normal in this respect, having the chloro group endo in the major product. These results are discussed in terms of the non-linear approach which carbenes and carbenoids may adopt when they are being inserted into double bonds.     

Synthesis and separation of the atropisomers of 2-(5-benzo[b]fluorenyl)-2′-hydroxy-1,1′-binaphthyl and related compounds

Several syn and anti atropisomers of 2-(5-benzo[b]fluorenyl)-2′-hydroxy-1,1′-binaphthyl and related compounds were synthesized from 1,1′-binaphthyl-2,2′-diol (BINOL). It was possible to separate the syn and anti atropisomers by silica gel column chromatography. The syn atropisomers are potential hetero-bidentate ligands for complex formation with metals. By starting from enantiomerically pure (R)-(+)-BINOL and (S)-(−)-BINOL, four optically active syn atropisomers and two anti atropisomers with high enantiomeric purity were obtained. The structures of two syn atropisomers and one anti atropisomer were established by X-ray structure analyses.     

Stereochemical course of acylation and aldol condensation in (4S)-4-methyl-2-benzyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones

Acylation of 1 leads to the syn derivatives 2. Traces of the anti isomers equilibrate to the syn isomers when stored in CHCl₃. Aldol condensation showed great diastereoselectivity, but racemization could not be avoided. The configuration of the new introduced stereogenic centres has been assigned on the basis of ¹H-NMR data and NOE measurements.     

Self-assembled coordination cage as a reaction vessel: triplet sensitized [2+2] photodimerization of acenaphthylene, and [4+4] photodimerization of 9-anthraldehyde

Inner cavity of Pd-nanocage has been used as a reaction vessel for performing triplet sensitized [2+2] photodimerization of acenaphthylene using water soluble xanthene dyes (Eosin Y and Rose Bengal) as sensitizers, and [4+4] photodimerization of 9-anthraldehyde. Although the [4+4] photodimerization of 9-anthraldehyde gave similar results to solution reaction, the xanthene dye sensitized [2+2] triplet state photodimerization of acenaphthylene encapsulated within Pd-nanocage yielded the syn dimer in quantitative yield. The results obtained from the triplet state [2+2] photodimerization of acenaphthylene within Pd-nanocage is remarkable given the fact that the photodimerization reaction when performed in methanol in the presence of Eosin Y and Rose Bengal gave the syn and anti dimers in the ratio 0.5 and 0.6, respectively. Preaggregation of molecules encapsulated inside Pd-nanocage in a syn fashion seems to be the governing factor for such a behavior.     

Aspects of stereocontrol in the L-Selectride reduction of 4-acyl-1,3-dioxolane derivatives

The application of L-Selectride, either alone or in combination with ZnCl₂, to aryl ketones 1, 8 and 11 resulted in highly anti-stereoselective reduction. In contrast, lactols 22 and 23 gave a moderate syn-preference using L-Selectride alone and a high syn-preference in the presence of ZnCl₂. Uniquely, high anti- stereoselectivity was observed in the reduction of o-anisyl lactol 37 with L-Selectride alone, which was switched to a high syn-preference when ZnCl₂ was present.     

A conformational study of [3.3](3,5)pyridinophane

A variable temperature ¹H NMR study of the [3.3](3,5)pyridinophane indicated that the syn(chair/chair) is more stable than syn(chair/boat) by 0.2 kcal/mol in solution, whereas the trimethylene bridges show disorder even at −150 °C in the solid state. A transition state search by ab initio MO calculations suggested two competitive conformational changes for syn(chair/chair)-syn(chair/boat) conversion via a bridge wobble or a ring inversion in the [3.3](3,5)pyridinophane.     

Dynamic molecular recognition in the generation of a new crystal-engineering motif: a unique case study of a dicarboxylic acid with a ditopic receptor favouring a polymeric over a dimeric hydrogen-bonded supramolecular complex

A new crystal-engineering motif has been developed where a ditopic receptor 1 shows a novel syn-syn hydrogen-bonded polymeric supramolecular complex (Fig. 4b) (instead of a 1:1 dimeric syn-syn or polymeric syn-anti complex) giving rise to a hydrogen-bonded stair-like polymeric ribbon structure between the binding groups of the receptor pyridine amide and the carboxyl groups of the guest substrate.     

Facile synthesis of various substituted taurines,especially syn- and anti-1,2-disubstituted taurines,from nitroolefins

Taurine and substituted taurines present a group of important structural elements in many natural products. Various substituted taurines, including 1- and 2-substituted, 1,1-, syn-1,2-, and anti-1,2-disubstituted taurines, were synthesized from the corresponding nitroolefins via Michael addition with thioacetic acid, oxidation with peroxyformic acid, and the catalytic hydrogenation under the catalysis of palladium on carbon or platinum dioxide. It is a general, versatile, and salt-free method for the preparation of substituted taurines, especially for syn- and anti-1,2-disubstituted taurines and some taurines with more bulky substituents. The stereostructures of both syn- and anti-1,2-disubstituted taurines were deduced from the nitroalkyl thioacetates in the Michael addition, which were identified via the Karplus equation analysis and computational analysis, and finally confirmed by the XRD single crystal analysis. The diastereoselectivity in the Michael addition was rationalized with the Cram rule.     

Diastereoselective synthesis of γ-hydroxy α,β-epoxyesters and their conversion into β-hydroxy α-sulfenyl γ-butyrolactones

The diastereoselectivity of the nucleophilic epoxidation of γ-hydroxy-α,β-unsaturated esters has been studied. The γ-hydroxy-α,β-unsaturated esters were obtained through treatment of ethyl (E)-4-oxo-2-butenoate with the corresponding Grignard reagent and were used as a racemic mixture. The resulting γ-hydroxy α,β-epoxyesters were treated with thiophenol for transformation into α-phenylsulfanyl trisubstituted γ-butyrolactones. The syn,syn-lactones isomerize easily in basic media into the syn,anti structures. In order to explain this interconversion, a retroaldol-aldol sequence has been proposed and a sulfur-oxygen interaction has been invoked to explain the syn stereochemical preference of the α-sulfured aldols resulting from the intramolecular aldol reaction.     

Stereochemistry of the addition of dialkyl phosphites to (S)-N,N-dibenzylphenylglycinal

The addition of various dialkyl phosphite derivatives to (S)-N,N-dibenzylphenylglycinal 6 led to the preponderance of anti over syn diastereoisomers: from 75:25 when NEt₃ or Ti(OiPr)₄ were used to 51:49 for Li or Mg salts. In the NEt₃-catalysed reaction, partially racemised phosphonates were formed, while enantiomeric products were obtained after addition of lithium O,O-dimethylphosphonate to (S)-6 at −70°C. Because the syn-isomers were found to be resistant to O-benzoylation, mixtures of diastereoisomers were easily separated after esterification of the anti products. Hydrogenation of the syn-phosphonates in the presence of Boc₂O gave enantiomeric dialkyl N-Boc-2-amino-1-hydroxy-2-phenylethylphosphonates—phosphonate analogues of the docetaxel C-13 side chain.     

Chiral base-catalyzed aldol reaction of trimethoxysilyl enol ethers: effect of water as an additive on stereoselectivities

An aldol reaction of trimethoxysilyl enol ether catalyzed by lithium binaphtholate is described. The aldol reaction of trimethoxysilyl enol ether derived from cyclohexanone under anhydrous conditions predominantly afforded the anti-aldol adduct with moderate enantioselectivity, whereas the reaction under aqueous conditions predominantly resulted in the syn-adduct and the enantioselectivity of the syn-adduct was considerably improved. The best enantioselectivity was obtained in the reaction of trimethoxysilyl enol ether derived from 1-indanone with cyclohexanecarboxaldehyde (97% ee (syn)). This is the first example of an aldol reaction of trimethoxysilyl enol ether catalyzed by a chiral base.     

Trading N and O. Part 4: Asymmetric synthesis of syn-β-substituted-α-amino acids

A total of nine enantiopure syn-β-substituted-α-amino acids have been synthesised, comprising both syn-β-hydroxy-α-amino acids and syn-β-fluoro-α-amino acids. The key step in the synthetic strategy towards these syn-β-substituted-α-amino acids involves a stereospecific rearrangement, which proceeds via the intermediacy of the corresponding aziridinium ions. The requisite enantiopure syn-α-hydroxy-β-amino esters were prepared via asymmetric aminohydroxylation of the corresponding α,β-unsaturated esters followed by epimerisation of the resultant anti-α-hydroxy-β-amino esters at the C(2)-position. Subsequent activation of the α-hydroxy moiety as a leaving group followed by displacement by the β-amino substituent gave the corresponding aziridinium species. Regioselective in situ ring-opening of the aziridinium intermediates with either water or fluoride gave the corresponding syn-β-hydroxy-α-amino ester or syn-β-fluoro-α-amino ester, respectively, and N-deprotection and ester hydrolysis afforded the target syn-β-substituted-α-amino acids as single diastereoisomers in good overall yield.     

Triplet-triplet absorption and polarization spectra of some syn-dioxabimanes

The triplet-triplet (T-T) absorption and polarization, singlet-singlet (S-S) absorption, and fluorescence spectra of syn-(methyl, hydrogen), syn-(tetramethylene), syn-(methyl, chloro)bimane, as well as those of syn-(phenyl, chloro), syn-(methyl, phenyl), and syn-(benzo)bimane were measured as part of a study of the factors that presumably control the laser action properties of the syn-bimanes.The syn-bimanes exhibit T-T absorption in the violet-blue/green portion of the spectrum and show two differently polarized transitions. A red shift in the S-S and T-T transition bands for a phenylbimane is dependent on the position of substitution (R₁ or R₂) and on the polarization of the bands. As substitution (R₁) along the long axis reduces T-T absorption over the fluorescence spectral region there is an improvement in laser action properties.Photoselection spectroscopy is briefly reviewed. Spectral arrangements and their polarizations (lasing constellations) of low-energy electronic transitions (S-S, T-T and fluorescence) that yield low T-T absorption within the fluorescence (laser action) spectral region and their correlation with molecular structure substituent effects are discussed.anti-Bimanes are proposed as possible phosphorescence laser materials.     

Stereochemical leakage mechanisms for tricarbonyl(dienyl)iron cations

ψ-Endo to ψ-exo leakage during solvolysis of a ψ-endo-dienol—Fe(CO)₃ dinitrobenzoate ester does not proceed via a syn, syn-cis-dienyl—Fe(CO)₃ cation. The most probable leakage mechanism involves non-stereospecific ionization of the dinitrobenzoate ester. syn,syn-cis-Dienyl—Fe(CO)₃ cations are formed from ψ-exo-dienol—Fe(CO)₃ complex during chromatography on grade I neutral alumina.     

Electrochemically driven stereoselective approach to syn-1,2-diol derivatives from vinylarenes and DMF

We have developed an electrochemically driven strategy for the stereoselective synthesis of protected syn-1,2-diols from vinylarenes with N,N-dimethylformamide (DMF). The newly developed system obviates the need for transition metal catalysts or external oxidizing agents, thus providing an operationally simple and efficient route to an array of protected syn-1,2-diols in a single step. This reaction proceeds via an electrooxidation of olefin, followed by a nucleophilic attack of DMF. Subsequent oxidation and nucleophilic capture of the generated carbocation with a trifluoroacetate ion is proposed, which gives rise predominantly to a syn-diastereoselectivity upon the second nucleophilic attack of DMF.

An electrochemical method that provides an operationally simple synthesis of masked syn-1,2-diols from styrenes and DMF has reported. The TFA ion is engaged in the formation of a key intermediate, which gives rise predominantly to syn-selectivity.     

Propellanes—LII : The reaction of conjugated dienic propellanes with singlet oxygen

The reactions of propellanes containing one or two cyclohexadiene rings with singlet oxygen take the course of exclusive syn-attack with respect to a hetero-ring containing two CO groups. When only one or no CO group is found in the hetero-ring, both syn- and anti-attack occur. The former course is interpreted in terms of secondary orbital interactions which stabilize the transition state for syn-attack.     

Synthesis and spectroscopic studies of highly fluorescent,solvatochromic diastereomers with differentially stacked bithiophene-substituted quinoxaline rings

Diastereomeric C-shaped molecules containing closely stacked bithiophene-substituted quinoxaline rings were synthesized and characterized by NMR, UV–vis absorption, and fluorescence spectroscopy. The unique geometry of each diastereomer resulted in different degrees of π-overlap between the bithiophene-substituted quinoxaline ring chromophores, modulating their spectroscopic properties. The donor-acceptor nature of this chromophore gave rise to its positive solvatochromism. ¹H NMR and UV–vis absorption spectroscopy confirmed the existence of π-π interactions in the ground state between the quinoxaline rings in both molecules but between the bithiophene rings only in the syn isomer. They exhibited significant emission maxima bathochromic shifts, a strong, positive solvatochromism, increased band broadening, and larger Stokes shifts when compared to a compound with an unstacked chromophore. Additionally, the syn isomer consistently showed λ_max,em value red-shifts and larger band broadening and Stokes shifts compared to the anti isomer due to the greater π-overlap in the syn isomer.     

Internal rotation and framework relaxation in ethene thiol

New and existing data on the ground and excited CS torsional states of the stable rotamers of ethene thiol have been analysed to give a potential function for internal rotation around the CS bond. The barrier between the syn and anti rotamers is found to be 800 cm^?1 and that at the planar anti conformation itself to be 12 cm^?1. the syn conformation is 50 cm^?2 more stable than the ‘quasi-planar’ anti conformation Satisfactory reproduction of the observed trends in rotational constants with torsional excitations has been achieved by introducing extensive relaxation of the CCS angle and the CS bond length during internal rotation. The CCS angle reduces by up to 5° v'hilst the CS bond length increases by up to 0.02 A during rotation from the syn to anti conformation. The use of ab initio M.O. calculations to provide an indication of the most significant aspects of structure relaxation is described.